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Authors: Pallavi Subhraveti Ron Caspi Peter Midford Peter D Karp An online version of this diagram is available at BioCyc.org. Biosynthetic pathways are positioned in the left of the cytoplasm, degradative pathways on the right, and reactions not assigned to any pathway are in the far right of the cytoplasm. Transporters and membrane proteins are shown on the membrane. Ingrid Keseler Periplasmic (where appropriate) and extracellular reactions and proteins may also be shown. Pathways are colored according to their cellular function. Gcf_000686005Cyc: Phyllobacterium sp. UNC302MFCol5.2 Cellular Overview Connections between pathways are omitted for legibility. Anamika Kothari lipid II (meso diaminopimelate 3-O-L-lysyl-1-O- containing) phosphate phosphatidylglycerol FtsW RS0112300 MprF lipid II (meso 3-O-L-lysyl-1-O- diaminopimelate phosphatidylglycerol containing) phosphate Amino Acid Degradation Storage Compound Biosynthesis Polyprenyl Biosynthesis Hormone Biosynthesis Aromatic Compound Biosynthesis Macromolecule Modification tRNA-uridine 2-thiolation ATP N 6 -(3-methylbut- ditrans,octacis- ditrans,octacis- a 1-acyl-2- a [DNA]-3'- a 5'-phospho- a [protein]-L- and selenation (bacteria) an L-cysteinyl- 34 di-trans,poly-cis indole-3-acetate biosynthesis L-valine degradation I a sulfurated adenosylcobinamide a purine a [glutamine- an L-asparaginyl- a cytidine polyhydroxybutanoate biosynthesis chorismate biosynthesis I L-leucine degradation I L-arginine degradation V L-histidine degradation II L-tryptophan degradation to 2-en-1-yl)- undecaprenyldiphospho- undecaprenyldiphospho- arachidonoyl- hydroxyl [DNA] Asn Cys lys methionine L-tyrosine degradation I ATP [tRNA ] [tRNA ] ATP roseoflavin Ile2 Metabolic Regulator Biosynthesis -undecaprenyl biosynthesis 3-(4-hydroxyphenyl) Alcohol Degradation [sulfur carrier] 37 ribonucleoside synthetase]- in tRNA peptide- (arginine deiminase pathway) 2-amino-3-carboxymuconate adenosine N-acetyl-(N- N-acetyl-(N- sn-glycerol 5'-phosphate Aminoacyl-tRNA Charging glutaminyl-tRNA gln biosynthesis via transamidation phosphate biosynthesis IV (bacteria) D-erythrose pyruvate biosynthesis cys in tRNA 5'-triphosphate acetylglucosaminyl) acetylglucosaminyl) 3-phosphate CTP L-tyrosine methionine acetyl-CoA ADP val semialdehyde ATP-dependent ppGpp metabolism (2E,6E)-farnesyl (indol-3-yl) 4-phosphate leu tyr his glycerol and glycerophosphodiester degradation muramoyl-L-alanyl-γ- muramoyl-L-alanyl- (S)-S-oxide glycine betaine IPP 3-deoxy-7- cysteine ATP synthase arg aminoacyl-tRNA aminoacyl-tRNA tRNA diphosphate acetonitrile histidine trp tRNA (N6-isopentenyl bifunctional β γ DNA ligase: bifunctional reductase acetyl-CoA C- nitrile phosphoheptulonate tyr branched-chain branched-chain bifunctional D-isoglutaminyl-N-( - -D-isoglutaminyl- phosphatidate bifunctional [glutamine hydrolase: hydrolase: lysidine(34) glu biosynthesis I (Gram- desulfurase: subunit C: adenosine(37)-C2)- adenosylcobinamide BR48_RS0114820 MsrA: msrA pppGpp acetyltransferase: hydratase: bifunctional amino acid aspartate arginine ammonia- tryptophan 2,3- glycerol D-asparaginyl)-L-lysyl- N-(β-D-asparaginyl) synthetase] BR48_RS0122835 BR48_RS0122835 riboflavin kinase/ synthetase negative bacteria) synthase class II: sufS BR48_RS25055 amino acid methylthiotransferase kinase/ cytidylyltransferase: BR48_RS0105330 isoprenyl nthB nthA aspartate aminotransferase: transaminase/ deiminase: lyase: hutH dioxygenase: D-alanyl-D-alanine -L-lysyl-D-alanine adenylyltransferase/ cisplatin damage FAD synthetase: TilS: tilS peptide- (indol-3-yl) 3-deoxy- BR48_RS0113025 cysteine desulfurase: [+ 7 isozymes] aminotransferase: urocanate MiaB: miaB adenosylcobinamide- BR48_RS0118130 aminoacyl-tRNA aminoacyl-tRNA choline [+ 2 isozymes] transferase: transaminase/ BR48_RS0122710 aspartate 4- arcA kynA L-proline degradation I [glutamine synthetase]- response ATP- BR48_RS0104475 methionine D-arabino- ATP BR48_RS0122710 N-Formyl-L- phosphate phosphatidate hydrolase: hydrolase: bifunctional (p)ppGpp choline acetamide BR48_RS0111395 succinate adenylyl-L-tyrosine dependent BR48_RS0118125 aspartate 4- decarboxylase: urocanate kynurenine a glycerophosphodiester 34 (S)-S-oxide dehydrogenase: heptulosonate an [L-cysteine branched-chain branched-chain guanylyltransferase: monofunctional monofunctional cytidylyltransferase: BR48_RS0108530 BR48_RS0108530 a lysidine synthetase/guanosine- acetoacetyl-CoA amidase: decarboxylase: BR48_RS0118820 L-citrulline dehydrogenase, phosphorylase: DNA ligase: roseoflavin reductase an L-glutamyl- 7-phosphate desulfurase]-S- amino acid amino acid hydratase: pro glycerol cobU biosynthetic biosynthetic BR48_RS0110235 in tRNA Ile2 3',5'-bis(diphosphate) 3'- betA di-trans,octa-cis BR48_RS0115470 BR48_RS0118820 hydrophobic BR48_RS0102920 BR48_RS0116220 adenine MsrA: msrA [tRNA Gln ] 3-dehydroquinate sulfanyl-L-cysteine aminotransferase: aminotransferase: bifunctional BR48_RS0106840 peptidoglycan peptidoglycan a protein-L- pyrophosphohydrolase: betaine aldehyde -undecaprenyl [+ 2 isozymes] bifunctional glycerophosphodiester membrane anchor adenosyl- dinucleotide synthase: bifunctional BR48_RS0103245 4-methyl-2-BR48_RS0103245 aspartate 4-imidazolone- transglycosylase: transglycosylase: tRNA Asn a tRNA Cys Asp-tRNA(Asn) BR48_RS0102465 diphosphate ornithine proline glycerol kinase phosphodiesterase: protein: sdhD cobinamide a CDP-1-acyl- asn cys methionine- betaine-aldehyde aspartate 5-propanoate mtgA mtgA a [glutamine /Glu-tRNA(Gln) (3R)-3- undecaprenyl- (indol-3-yl)acetate BR48_RS0110835 3-methyl-2- oxopentanoate transaminase/ carbamoyltransferase: L-kynurenine dehydrogenase/L- GlpK: glpK BR48_RS0118090 phosphate a purine 2-arachidonoyl- [DNA] (S)-S-oxide dehydrogenase: transaminase/ 6 synthetase]-O gln amidotransferase hydroxybutanoyl- poly-[(R)-3- diphosphate a [TusA sulfur- oxobutanoate aspartate 4- argF imidazolonepropionase: glutamate gamma- N -(3-methylbut- ribonucleoside glycerol betB 3-dehydroquinate aspartate 4- 5'-deoxyadenosine an unsulfurated 4 -(5'-adenylyl) subunit GatB: gatB CoA hydroxybutanoate] phosphatase: carrier protein]-S- decarboxylase: BR48_RS0106825 semialdehyde 2-en-1-yl)-2- met 5'-diphosphate a peptidoglycan di-trans,octa-cis a peptidoglycan di-trans,octa-cis GTP ppGpp 3-(4- [sulfur carrier] -L-tyrosine Asp-tRNA(Asn) decarboxylase: sulfanyl-L-cysteine BR48_RS0112475 sn-glycerol 3-phosphate (methylsulfanyl) dimer (E. faeciums) -undecaprenyl dimer (E. faecium -undecaprenyl Asp-tRNA(Asn) glycine betaine BR48_RS0108145 type II 3- carbamoyl dehydrogenase 3-(4- BR48_RS0112475 3-methylbutanoyl- hydroxyphenyl) N-formimino- 37 /Glu-tRNA(Gln) class I poly(R)- di-trans,octa-cis dehydroquinate L-ornithine PutA: putA adenosine diphosphate , tetrapeptide) diphosphate /Glu-tRNA(Gln) hydroxyphenyl) CoA pyruvate phosphate L-glutamate (S)-1-pyrroline- glycerol-3-phosphate amidotransferase nucleoside- bifunctional (p)ppGpp hydroxyalkanoic -undecaprenyl dehydratase: aroQ isobutanoyl-CoA 3-hydroxy- in tRNA amidotransferase: pyruvate isovaleryl-CoA glutamine- 5-carboxylate dehydrogenase: subunit GatB: gatB diphosphate kinase: synthetase/guanosine- acid synthase: phosphate 4-hydroxyphenylpyruvate formimidoylglutamate L-kynurenine gatC gatA a [TusD sulfur- BR48_RS0107715 [+ 7 isozymes] phaC 3-dehydroshikimate dehydrogenase: dioxygenase: hppD hydrolyzing deiminase: F0F1 ATP a 5-phosphooxy- BR48_RS0102030 3',5'-bis(diphosphate) 3'- + + carrier protein]-S- BR48_RS0102795 carbamoyl- kynureninase: ditrans,octacis- a peptidoglycan with an [HPr]- phosphoenol a carboxy- a mature a [glutamine 4-methyl-5-(2- L-rhamnulose succinate (E)-4-hydroxy-3- a protein-L- H H pyrophosphohydrolase: BR48_RS0106820 menadione NADH H + synthase ammonium L-glutamyl- shikimate sulfanyl-L-cysteine kynU DHAP undecaprenyldiphospho- (L-alanyl-γ-D-glutamyl- adenylated- cys peptidoglycan synthetase]-O phosphooxyethyl) 1-phosphate methylbut-2-en- methionine- poly-[(R)-3- 3-methylcrotonyl- homogentisate phosphate L-histidine pyruvate (n) HMP-PP semialdehyde ATP [tRNA Gln ] BR48_RS0102465 dehydrogenase: N-formyl- β 4 thiazole 1-yl diphosphate synthase: L-glutamate-5- N-acetyl-(N-acetyl- -D- L-lysyl-D-alanyl-D- [ThiS sulfur- (meso-DAP -(5'-adenylyl) NAD-dependent biotin flavodoxin- (R)-S-oxide hydroxybutanoate] methylacrylyl-CoA CoA 3-hydroxyanthranilate peptide- BR48_RS0108640 homogentisate carA carB L-glutamate semialdehyde Aromatic Compound glucosaminyl)muramoyl- alanine) pentapeptide carrier protein] containing) -L-tyrosine succinate- a reduced Asp-tRNA(Asn) methylcrotonoyl- phosphoenolpyruvate- bifunctional dependent methionine a [TusE sulfur enoyl-CoA 1,2-dioxygenase: N-formylglutamate Degradation L-alanyl-γ-D-glutamyl-L- NADH-quinone semialdehyde H O c-type thiamine (E)-4-hydroxy- (R)-S-oxide 2 /Glu-tRNA(Gln) GDP shikimate CoA carboxylase: BR48_RS0116270 carbamate bifunctional lysyl-D-alanyl-D-alanine -protein oxidoreductase: rhamnulose-1- dehydrogenase: biotin--[acetyl-CoA- 34 carrier protein]-S hydratase: amidohydrolase: lytic phosphate 3-methylbut- cytochrome amidotransferase a uridine in tRNA BR48_RS0102800 proline 4-hydroxyphenylacetate phosphotransferase: ptsP cysteine desulfurase: BR48_RS0117355 bifunctional [glutamine phosphate aldolase/ reductase RS0119895 an oxidized -sulfanylcysteine BR48_RS0117195 4-maleyl- BR48_RS0110080 synthase: BR48_RS0116570 carboxylase] ligase: subunit GatB: gatB shikimate kinase: [+ 2 isozymes] dehydrogenase/L- degradation BR48_RS0111395 transglycosylase synthetase] short-chain 2-enyl- MsrB: msrB O c-type acetoacetate 2-amino-3- phosphoenolpyruvate-
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    Proc. Natl. Acad. Sci. USA Vol. 88, pp. 6580-6584, August 1991 Biochemistry Signal transduction convergence: Phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence RICHARD M. O'BRIEN, MARIA T. BONOVICH, CLAUDE D. FOREST, AND DARYL K. GRANNER* Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615 Communicated by Charles R. Park, April 29, 1991 ABSTRACT Pbosphoenolpyruvate carboxykinase describe such an element here and in so doing report an (PEPCK) governs the rate-limiting step in gluconeogenesis. example of signal transduction convergence: the inhibitory Glucocorticoids and cAMP increase PEPCK gene transcription effects of phorbol esters and insulin on the PEPCK gene, and gluconeogenesis, whereas insulin and phorbol esters have which start with the generation of unique signals, are medi- the opposite effect. Insulin and phorbol esters are dominant, ated through a common 10-base-pair (bp) sequence. since they prevent cAMP and glucocorticoid-stinulated tran- scription. Basal promoter elements and hormone response elements for cAMP, glucocorticoids, and insulin have been MATERIALS AND METHODS defined in previous studies. By using stable transfectants containing a variety of different PEPCK-chloramphenicol Plasmid Construction. The construction of a series of acetyltransferase fusion gene constructs, a phorbol ester re- reporter constructs containing 5' deletion mutations of the sponse sequence, located between positions -437 and -402 PEPCK promoter ligated to the chloramphenicol acetyltrans- relative to the transcription start site, was identified. This ferase (CAT) gene has been described (23). Plasmid TKC-VI region coincides with the insulin response sequence that has (provided by T.
  • Identification of Active Molecules Against Mycobacterial Shikimate

    Identification of Active Molecules Against Mycobacterial Shikimate

    Identification of active molecules against Mycobacterial Shikimate Kinase from Chemical library and their affinity with different domains Sapna Pandey1, Ekta Dhamija1, Sanjay Kumar1, Pragya Yadav1, Tadigopula Narender1, Arnava Dasgupta1, Ravishankar Ramachandran1, and KISHORE SRIVASTAVA1 1Central Drug Research Institute November 9, 2020 Abstract Tuberculosis (TB), regardless of being the oldest disease is still a menace that humans have not been able to control. With the advancement in the drug discovery programme, target-based drug discovery appears to be one of the promising techniques for the development of future therapeutics. It involves identifying an essential gene involved in the pathogenesis of the disease and then targeting the protein against a defined chemical library. Shikimate kinase is one such validated target in mycobacterium. It is vital for the growth of bacteria and is absent in mammals, making it an ideal drug target. Here 6427 compounds were screened through structure based virtual screening where compound S-014-1049 was found active against H37Rv and proven non-cytotoxic in in vitro studies. It specifically binds to the core domain of MTSK. Introduction The development of drug resistance is a severe threat to public health. Presently, use of antibiotics targets bacterial structure and essential functions. Due to the well-identified anti-mycobacterial resistance, there has been an increased interest in the discovery of novel drugs to target other essential processes of bacterial survival. Currently, target-based drug screening is promising and efficient way for development of therapeutic agents. In recent years, extensive efforts have been made for the discovery of inhibitors of enzymes involved in the biosynthesis of aromatic amino acids.
  • Structures, Functions, and Mechanisms of Filament Forming Enzymes: a Renaissance of Enzyme Filamentation

    Structures, Functions, and Mechanisms of Filament Forming Enzymes: a Renaissance of Enzyme Filamentation

    Structures, Functions, and Mechanisms of Filament Forming Enzymes: A Renaissance of Enzyme Filamentation A Review By Chad K. Park & Nancy C. Horton Department of Molecular and Cellular Biology University of Arizona Tucson, AZ 85721 N. C. Horton ([email protected], ORCID: 0000-0003-2710-8284) C. K. Park ([email protected], ORCID: 0000-0003-1089-9091) Keywords: Enzyme, Regulation, DNA binding, Nuclease, Run-On Oligomerization, self-association 1 Abstract Filament formation by non-cytoskeletal enzymes has been known for decades, yet only relatively recently has its wide-spread role in enzyme regulation and biology come to be appreciated. This comprehensive review summarizes what is known for each enzyme confirmed to form filamentous structures in vitro, and for the many that are known only to form large self-assemblies within cells. For some enzymes, studies describing both the in vitro filamentous structures and cellular self-assembly formation are also known and described. Special attention is paid to the detailed structures of each type of enzyme filament, as well as the roles the structures play in enzyme regulation and in biology. Where it is known or hypothesized, the advantages conferred by enzyme filamentation are reviewed. Finally, the similarities, differences, and comparison to the SgrAI system are also highlighted. 2 Contents INTRODUCTION…………………………………………………………..4 STRUCTURALLY CHARACTERIZED ENZYME FILAMENTS…….5 Acetyl CoA Carboxylase (ACC)……………………………………………………………………5 Phosphofructokinase (PFK)……………………………………………………………………….6